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BACKGROUND: Few studies have explored associations between adaptive functioning and cognition in adolescents with early-onset schizophrenia spectrum disorders (EOS). METHODS: Adaptive functioning, cognition, positive, negative, and general symptoms were characterized in adolescents with EOS and healthy controls. A modified scale of negative, respectively, general symptoms was used. Bivariate analyses identified correlates of adaptive functioning to be included in multivariate analysis. RESULTS: Adolescents with EOS showed significant impairments of social- and neurocognitive functions (-0.86 < Cohen´s ds < -0.58) and adaptive functioning (Cohen´s d = -2.23). Visual memory, verbal working memory, processing speed, reaction time, social cognition, and modified negative and general symptoms correlated significantly with adaptive functioning. The multiple regression analysis revealed only verbal working memory as uniquely associated with adaptive functioning (explaining 22.7 % of its variance). Verbal working memory also associated significantly with adaptive functioning in the context of the nonsignificant modified negative and the significant modified general symptoms dimension. CONCLUSIONS: Adolescents with first-episode EOS had large impairments in adaptive functioning and moderate to large cognitive deficits. Verbal working memory was an important associate to concurrent adaptive functioning and may be a treatment target for trials to improve cognitive and adaptive functioning in adolescents with EOS.
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BACKGROUND: Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are developmental disorders with shared clinical characteristics such as cognitive impairments and impulsivity. Impulsivity is a core feature of ADHD and an important factor in aggression, violence, and substance use in schizophrenia. Based on the hypothesis that schizophrenia and ADHD represent a continuum of neurodevelopmental impairments, the aim was to identify overlapping and disease specific forms of impulsivity. METHODS: Adolescents between 12 and 17 years of age were assessed with the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime Version. Subjects with early-onset, first-episode schizophrenia spectrum disorders (EOS) (N = 29) or ADHD (N = 29) and healthy controls (N = 45) were compared on two performance measures (Information Sampling Task, Stop Signal Task) and a subjective personality trait measure of impulsivity (Barratt Impulsiveness Scale, Version 11 (BIS-11)). RESULTS: Significantly increased reflection impulsivity was observed in ADHD but not in the EOS group. No significant response inhibition deficits (stop signal reaction time) were found in the two clinical groups. The ADHD and the EOS group showed significantly increased motor, attentional, and non-planning subtraits of impulsivity. CONCLUSIONS: Impaired pre-decisional information gathering appeared to be specific for ADHD while the information gathering was not significantly reduced in subjects with EOS. Neither the ADHD nor EOS group showed impaired response inhibition but shared increased personality subtraits of attentional, non-planning, and motor impulsivity although the latter was significantly more pronounced in ADHD. These increased subtraits of impulsivity may reflect diagnostic non-specific neurodevelopmental impairments in ADHD and EOS in adolescence.
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Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Atenção , Comportamento Impulsivo , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Adolescente , Estudos de Casos e Controles , Dinamarca , Feminino , Humanos , Masculino , Análise Multivariada , Testes Neuropsicológicos , Personalidade/fisiologia , Tempo de Reação , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The neurodevelopmental hypothesis of psychosis suggests that disrupted white matter (WM) maturation underlies disease onset. In this longitudinal study, we investigated WM connectivity and compared WM changes between individuals at ultra-high-risk for psychosis (UHR) and healthy controls (HCs). METHOD: Thirty UHR individuals and 23 HCs underwent MR diffusion tensor imaging before and after 12 months of non-manualized standard care. Positive and negative symptoms and level of functioning were assessed. Tract-based spatial statistics were employed. RESULTS: During 12 months, none of the UHR individuals transitioned to psychosis. Both UHR individuals and HCs increased significantly in fractional anisotropy (FA). UHR individuals showed significant FA increases predominantly in the left superior longitudinal fasciculus (SLF) (P = 0.01), and HCs showed significant FA increases in the left uncinate fasciculus (P = 0.03). Within UHR individuals, a significant positive correlation between FA change and age was observed predominantly in the left SLF (P = 0.02). Within HCs, no significant correlation between FA change and age was observed. No significant correlations between baseline FA and clinical outcomes were observed; however, FA changes were significantly positively correlated to changes in negative symptoms (P = 0.04). CONCLUSION: As normal brain maturation occurs in a posterior to frontal direction, our findings could suggest disturbed WM maturation in UHR individuals.
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Encéfalo/diagnóstico por imagem , Sintomas Prodrômicos , Transtornos Psicóticos/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Anisotropia , Encéfalo/crescimento & desenvolvimento , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Transtornos Psicóticos/psicologia , Risco , Adulto JovemRESUMO
BACKGROUND: Attention deficits have been frequently reported in schizophrenia. It has been suggested that treatment with second-generation antipsychotics can ameliorate these deficits. In this study, the influence of 6 months treatment with quetiapine, a compound with less affinity for dopamine D2 receptors than for serotonergic 5-HT2A receptors, on electrophysiological parameters of attention was investigated in a group of antipsychotic-naïve, first-episode schizophrenia patients compared with a group of age- and gender-matched healthy controls. METHOD: A total of 34 first-episode, antipsychotic-naïve patients with schizophrenia and an equal number of healthy controls were tested in a selective attention and a typical mismatch negativity (MMN) paradigm at baseline and after 6 months. The patients were treated with quetiapine according to their clinical needs during the period between baseline and follow-up, whereas controls received no treatment. RESULTS: Patients showed lower MMN and P200 amplitude than healthy controls in the selective attention paradigm at baseline, while this was not the case for MMN of the typical MMN paradigm. Interestingly, after 6 months treatment, this MMN deficit was only ameliorated in patients treated with above median dosages of quetiapine. Patients had lower P3B amplitude, yet showed similar levels of processing negativity and N100 amplitude compared with healthy controls, both at baseline and follow-up. CONCLUSIONS: The results indicate that deficits in MMN, P200 and P3B amplitude are present at early stages of schizophrenia, although depending on the paradigm used. Furthermore, the results indicate that 6 months quetiapine treatment ameliorates MMN but not P3B deficits, and only in those subjects on higher dosages.
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Antipsicóticos/farmacologia , Atenção/fisiologia , Potenciais Evocados/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Fumarato de Quetiapina/farmacologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Adulto , Antipsicóticos/administração & dosagem , Eletroencefalografia , Potenciais Evocados/efeitos dos fármacos , Feminino , Humanos , Masculino , Fumarato de Quetiapina/administração & dosagemRESUMO
BACKGROUND: Individuals at ultra-high-risk (UHR) for psychosis present with emerging symptoms and decline in functioning. Previous univariate analyses have indicated widespread white matter (WM) aberrations in multiple brain regions in UHR individuals and patients with schizophrenia. Using multivariate statistics, we investigated whole brain WM microstructure and associations between WM, clinical symptoms, and level of functioning in UHR individuals. METHODS: Forty-five UHR individuals and 45 matched healthy controls (HCs) underwent magnetic resonance diffusion tensor imaging (DTI) at 3 Tesla. UHR individuals were assessed with the Comprehensive Assessment of At-Risk Mental States, Scale for the Assessment of Negative Symptoms, and Social and Occupational Functioning Assessment Scale. Partial least-squares correlation analysis (PLSC) was used as statistical method. RESULTS: PLSC group comparisons revealed one significant latent variable (LV) accounting for 52% of the cross-block covariance. This LV indicated a pattern of lower fractional anisotropy (FA), axial diffusivity (AD), and mode of anisotropy (MO) concomitant with higher radial diffusivity (RD) in widespread brain regions in UHR individuals compared with HCs. Within UHR individuals, PLSC revealed five significant LVs associated with symptoms and level of functioning. The first LV accounted for 31% of the cross-block covariance and indicated a pattern where higher symptom score and lower level of functioning correlated to lower FA, AD, MO, and higher RD. CONCLUSIONS: UHR individuals demonstrate complex brain patterns of WM abnormalities. Despite the subtle psychopathology of UHR individuals, aberrations in WM appear associated with positive and negative symptoms as well as level of functioning.
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Transtornos Psicóticos/patologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Substância Branca/patologia , Adulto , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Transtornos Psicóticos/diagnóstico por imagem , Risco , Esquizofrenia/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
BACKGROUND: Deficient mismatch negativity (MMN) has been proposed as a candidate biomarker in schizophrenia and may therefore be potentially useful in early identification and intervention in early onset psychosis. In this study we explored whether deficits in the automatic orienting and reorienting responses, measured as MMN and P3a amplitude, are present in young adolescents with first-episode psychosis (FEP) and whether findings are specific to psychosis compared to young adolescents with attention deficit hyperactivity disorder (ADHD). METHOD: MMN and P3a amplitude were assessed in young adolescents (age 12-17 years) with either FEP (N = 27) or ADHD (N = 28) and age- and gender-matched healthy controls (N = 43). The MMN paradigm consisted of a four-tone auditory oddball task with deviant stimuli based on frequency, duration and their combination. RESULTS: Significantly less MMN was found in patients with psychosis compared to healthy controls in response to frequency and duration deviants. MMN amplitudes in the group of patients with ADHD were not significantly different from patients with psychosis or healthy controls. No significant group differences were found on P3a amplitude. CONCLUSION: Young adolescents with FEP showed impaired MMN compared to healthy controls while intermediate and overlapping levels of MMN were observed in adolescents with ADHD. The findings suggest that young FEP patients already exhibit pre-attentive deficits that are characteristic of schizophrenia albeit expressed on a continuum shared with other neuropsychiatric disorders.
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Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Percepção Auditiva/fisiologia , Potenciais Evocados P300/fisiologia , Potenciais Evocados Auditivos/fisiologia , Transtornos Psicóticos/fisiopatologia , Adolescente , Criança , Eletroencefalografia , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Schizophrenia is associated with profound cognitive and psychosocial impairments. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for diabetes and obesity treatment, and animal studies have indicated cognitive-enhancing effects. In this investigator-initiated, double-blind, randomized, placebo-controlled trial, we tested non-metabolic effects of exenatide once-weekly (Bydureon™) in obese, antipsychotic-treated patients with schizohrenia spectrum disorder. METHOD: Before and after 3 months of exenatide (N = 20) or placebo (N = 20) treatment, patients were assessed with the following: Brief Assessment of Cognition in Schizophrenia (BACS), Rey-Osterreith complex figure test (REY), Short-Form Health Survey (SF-36), Personal and Social Performance Scale (PSP) and the Positive and Negative Syndrome Scale (PANSS). We used BACS composite score as the main outcome measure. RESULTS: Repeated measures analysis of variance on BACS composite score showed significant effect of 'Time' (P < 0.001), no effect of 'Group' (P = 0.64) and no 'Time*Group' interaction (P = 0.77). For REY, SF-36, PSP and PANSS, only significant 'Time' effects were found. CONCLUSION: The non-significant results of this first clinical trial exploring non-metabolic effects of a long-acting GLP-1RA in patients with schizophrenia could reflect a general problem of translating cognitive-enhancing effects of GLP-1RAs from animals to humans or be explained by factors specifically related to schizophrenia spectrum patients with obesity such as antipsychotic treatment.
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Disfunção Cognitiva/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/farmacologia , Obesidade/tratamento farmacológico , Peptídeos/farmacologia , Esquizofrenia/tratamento farmacológico , Peçonhas/farmacologia , Adulto , Idoso , Antipsicóticos , Disfunção Cognitiva/etiologia , Comorbidade , Preparações de Ação Retardada , Método Duplo-Cego , Exenatida , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Peptídeos/administração & dosagem , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Falha de Tratamento , Peçonhas/administração & dosagem , Adulto JovemRESUMO
Studies across schizophrenia (SZ) and bipolar disorder (BD) indicate common transdiagnostic neurocognitive subgroups. However, existing studies of patients with long-term illness precludes insight into whether impairments result from effects of chronic illness, medication or other factors. This study aimed to investigate whether neurocognitive subgroups across SZ and BD can be demonstrated during early illness stages. Data from overlapping neuropsychological tests were pooled from cohort studies of antipsychotic-naïve patients with first-episode SZ spectrum disorders (n = 150), recently diagnosed BD (n = 189) or healthy controls (HC) (n = 280). Hierarchical cluster analysis was conducted to examine if transdiagnostic subgroups could be identified based on the neurocognitive profile. Patterns of cognitive impairments and patient characteristics across subgroups were examined. Patients could be clustered into two, three and four subgroups, of which the three-cluster solution (with 83% accuracy) was selected for posthoc analyses. This solution revealed a subgroup covering 39% of patients (predominantly BD) who were cognitively relatively intact, a subgroup of 33% of patients (more equal distributions of SZ and BD) displaying selective deficits, particularly in working memory and processing speed, and a subgroup of 28% (mainly SZ) with global impairments. The globally impaired group exhibited lower estimated premorbid intelligence than the other subgroups. Globally impaired BD patients also showed more functional disability than cognitively relatively intact patients. No differences were observed across subgroups in symptoms or medications. Neurocognitive results can be understood by clustering analysis with similar clustering solutions occurring across diagnoses. The subgroups were not explained by clinical symptoms or medication, suggesting neurodevelopmental origins.
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Transtorno Bipolar , Disfunção Cognitiva , Esquizofrenia , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Memória de Curto Prazo , Testes Neuropsicológicos , Análise por ConglomeradosRESUMO
Electroencephalography in patients with a first episode of psychosis (FEP) may contribute to the diagnosis and treatment response prediction. Findings in the literature vary due to small sample sizes, medication effects, and variable illness duration. We studied macroscale resting-state EEG characteristics of antipsychotic naïve patients with FEP. We tested (1) for differences between FEP patients and controls, (2) if EEG could be used to classify patients as FEP, and (3) if EEG could be used to predict treatment response to antipsychotic medication. In total, we studied EEG recordings of 62 antipsychotic-naïve patients with FEP and 106 healthy controls. Spectral power, phase-based and amplitude-based functional connectivity, and macroscale network characteristics were analyzed, resulting in 60 EEG variables across four frequency bands. Positive and Negative Symptom Scale (PANSS) were assessed at baseline and 4-6 weeks follow-up after treatment with amisulpride or aripiprazole. Mann-Whitney U tests, a random forest (RF) classifier and RF regression were used for statistical analysis. Our study found that at baseline, FEP patients did not differ from controls in any of the EEG characteristics. A random forest classifier showed chance-level discrimination between patients and controls. The random forest regression explained 23% variance in positive symptom reduction after treatment in the patient group. In conclusion, in this largest antipsychotic- naïve EEG sample to date in FEP patients, we found no differences in macroscale EEG characteristics between patients with FEP and healthy controls. However, these EEG characteristics did show predictive value for positive symptom reduction following treatment with antipsychotic medication.
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BACKGROUND: Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up. METHODS: About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery. RESULTS: There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = -0.34, N = 51, p = 0.01) in an explorative analysis. CONCLUSIONS: The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.
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Química Encefálica , Ácido Glutâmico/metabolismo , Giro do Cíngulo/metabolismo , Transtornos Psicóticos/metabolismo , Tálamo/metabolismo , Ácido gama-Aminobutírico/metabolismo , Adolescente , Adulto , Cognição , Disfunção Cognitiva/diagnóstico , Ácido Glutâmico/análise , Humanos , Testes Neuropsicológicos , Prognóstico , Psicopatologia , Transtornos Psicóticos/psicologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem , Ácido gama-Aminobutírico/análiseRESUMO
The sensory gating deficits in schizophrenia have been theorized to associate with increased distractibility. We explore the potential associations between sensory and sensorimotor gating and subjective and objective indices of distraction in healthy subjects. Forty healthy males were assessed with the P50 suppression and pre-pulse inhibition of the startle reflex (PPI) paradigms. Additionally, a neurocognitive test battery was administered in a cross-over design: with/without auditory distraction. Significant effects of distraction were found in response inhibition, and verbal working memory and attention. Parameters from the PPI and P50 suppression paradigms were significantly associated with the distractor effects on strategy formation, cognitive inhibition and flexibility, visual short-term memory, and the level of subjective distraction. Subjectively reported distraction was significantly associated with verbal working memory and attention as well as executive and supervisory processes. Sensory and sensorimotor gating efficiency do not reflect the effect of distraction across executive and attention functions i.e. we did not observe a generalized distractor effect. Gating only related to the effect of distraction on strategy formation, cognitive inhibition and flexibility, as well as visual short term memory. Future studies should investigate if gating deficits affect the distractibility of the same specific cognitive functions in patients with schizophrenia.
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Atenção/fisiologia , Transtornos Cognitivos/psicologia , Inibição Psicológica , Memória de Curto Prazo/fisiologia , Filtro Sensorial/fisiologia , Estimulação Acústica/métodos , Adulto , Cognição , Transtornos Cognitivos/fisiopatologia , Estudos Cross-Over , Potenciais Evocados/fisiologia , Voluntários Saudáveis , Humanos , Masculino , Testes de Estado Mental e Demência , Inibição Pré-Pulso , Reflexo de Sobressalto/fisiologiaRESUMO
Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response. Sixty-six antipsychotic-naive first-episode schizophrenia patients and sixty-five healthy controls underwent extensive electrophysiological and neurocognitive test batteries. Patients were assessed on the Positive and Negative Syndrome Scale (PANSS) before and after 6 weeks of monotherapy with the relatively selective D2 receptor antagonist, amisulpride (280.3±159 mg per day). A reduced principal component space based on 19 electrophysiological variables and 26 cognitive variables was used as input for a Gaussian mixture model to identify subgroups of patients. With support vector machines, we explored the relation between PANSS subscores and the identified subgroups. We identified two statistically distinct subgroups of patients. We found no significant baseline psychopathological differences between these subgroups, but the effect of treatment in the groups was predicted with an accuracy of 74.3% (P=0.003). In conclusion, electrophysiology and cognition data may be used to classify subgroups of schizophrenia patients. The two distinct subgroups, which we identified, were psychopathologically inseparable before treatment, yet their response to dopaminergic blockade was predicted with significant accuracy. This proof of principle encourages further endeavors to apply data-driven, multivariate and multimodal models to facilitate progress from symptom-based psychiatry toward individualized treatment regimens.
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Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Processos Mentais/fisiologia , Esquizofrenia/classificação , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Adulto , Algoritmos , Amissulprida , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Eletroencefalografia/efeitos dos fármacos , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Feminino , Seguimentos , Humanos , Aprendizado de Máquina , Masculino , Processos Mentais/efeitos dos fármacos , Testes Neuropsicológicos/estatística & dados numéricos , Distribuição Normal , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Valores de Referência , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Sulpirida/análogos & derivados , Sulpirida/uso terapêuticoRESUMO
1. Which transmitters are primarily or secondarily involved in the pathogenesis of schizophrenia has been extensively studied during the last years. This review concentrates on the two systems, that most constantly have been found dysfunctioning in patients; that are the dopaminergic and glutamatergic systems. 2. Numerous neuropathological defects have been found in schizophrenia, but it is as yet unknown which changes are causative and which reflect maladaptive reactions. 3. All findings, however, involve the cortico-striato-thalamo-cortical circuits, which are central for attention and information processing. 4. The article focuses on the consequence of transmitter dysfunction for perception and for the ability of the individual to adapt to a constantly changing environment. Both clinical and experimental studies point to a primary/early cortical defect involving the glutamatergic system, and to a later developed intermittent hyperactivity of the dopaminergic system superimposed on a basal hypodopaminergic state. 5. The authors have previously demonstrated, how it is possible to potentiate mesolimbic dopaminergic activity by intermittent electrical stimulations of the cells in the ventral tegmental area, and that influence on the central mesolimbic dopamine cells is essential for the strengthened neuroplastic response. A changed neuroplastic response to environmental stimulation due to dopaminergic sensitization can explain how an episodic, subcortical hyperactivity can act on a basic glutamatergic and dopaminergic hypofunction to produce psychotic symptoms. Based on our own and others clinical and experimental findings, the "filter" hypothesis for schizophrenia and the state-dependence of schizophrenic symptoms, the authors present a hypothesis for spontaneous mesolimbic dopaminergic sensitization and progressive evolution of psychosis.
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Dopamina/metabolismo , Esquizofrenia/etiologia , Animais , Humanos , Esquizofrenia/metabolismoRESUMO
Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young healthy men by the use of identical paired stimuli. In this study, the exploration of the gating paradigm was extended with the addition of a mixed modality paradigm where three different pairs of identical stimuli (clicks, right median nerve electric stimulations and proprioceptive stimuli of changing load on a handheld weight) were presented over a 12-s cycle. In both modalities repeated measures analyses of variance demonstrated no effect of paradigm. This mixed-modality recording paradigm could be used in further experiments to examine gating deficits across modalities.
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Atenção/fisiologia , Potenciais Evocados Auditivos/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Nervo Mediano/fisiologia , Propriocepção/fisiologia , Tempo de Reação/fisiologia , Adulto , Córtex Cerebral/fisiologia , Estimulação Elétrica , Humanos , Masculino , Valores de Referência , Suporte de Carga/fisiologiaRESUMO
A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-processing deficits in schizophrenia. The relationship between gating of the mid-latency evoked potentials (EP) in the somatosensory and the auditory modalities has not been studied together before. In schizophrenia, we might expect the processing deficits to act on multiple modalities. We have examined the gating of median nerve somatosensory EP (SEP) following paired stimulation identical to the AEP P50 gating paradigm using interstimulus intervals (ISI) of 500, 750 and 1000 ms and the correlation of gating to the skin conductance orienting response (SCOR) in 20 healthy men. We measured mid-latency vertex components (SEP: P50, N65, P85 and N100; AEP: P30, N45, P50 and N80). The gating was most pronounced at ISI 500 ms where the SEP P50 and N100 gating were 0.59 and 0.37, respectively, as compared to a gating of 0.61 in P30, 0.33 in P50 and 0.45 in N80 in the AEP. Repetition effects in the two modalities were not correlated. AEP P50 gating was correlated to skin conductance level (SCL). The combination of recording repetition effects on the mid-latency EP in two modalities could provide a method for investigating if deficits of information processing in schizophrenia are cross-modal.
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Nível de Alerta/fisiologia , Potenciais Evocados Auditivos/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Resposta Galvânica da Pele/fisiologia , Adulto , Eletroencefalografia , Potenciais Evocados P300/fisiologia , Humanos , Masculino , Nervo Mediano , Modelos Neurológicos , Valores de Referência , Estatísticas não ParamétricasRESUMO
The schizotypal personality disorder is believed to be part of the schizophrenic spectrum of disorders including schizophrenic patients as well as some of their seemingly unaffected relatives with discreet symptoms. Spectrum-individuals are characterised by a genetic vulnerability for schizophrenia. The vulnerability is connected with neurocognitive deficits independent of clinical state. Some cognitive dysfunctions are unspecific and probably related to non-genetic brain damage. A consistent finding has, however, been poor performance in tasks involving information processing and attention. The findings point to the existence of specific sensory-perceptual deficits or a general attentional dysfunction. Identification of cognitive disturbances characteristic not only of schizophrenics, but also of schizotypal disordered and their relatives in the boundaries of schizophrenia, is relevant in order better to understand the pathogenetic mechanisms and treatment of schizophrenia. In the present review clinical data are analysed based on models of vulnerability and information processing with reference to a characterisation of the neuro-integrative deficits that form the core abnormalities of the spectrum.
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Atenção , Transtornos Cognitivos/etiologia , Esquizofrenia/complicações , Esquizofrenia/genética , Transtornos Cognitivos/diagnóstico , Humanos , Testes Neuropsicológicos , Mascaramento Perceptivo/fisiologia , Tempo de Reação , Sensibilidade e Especificidade , Percepção Visual/fisiologiaRESUMO
The malignant neuroleptica syndrome (MNS) and the serotonin syndrome (SS) can be impossible to differentiate. This case history describes clinical symptoms compatible with either MNS or SS in a 59-year-old schizophrenic male patient, who had been heavily medicated with antipsychotics for several years in close relation to initiation of new treatment with a SSRI compound. The case shows that it is important to have both syndromes in mind when chronically ill patients are treated with several medicaments.
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Síndrome Maligna Neuroléptica/diagnóstico , Síndrome da Serotonina/diagnóstico , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversosRESUMO
The great diversity of schizophrenic symptoms rules out one simple etiological explanation. However,impairment of information processing, including disruption of sensorimotor gating, is a consistent finding in schizophrenic patients. Dysfunction in sensorimotor gating is believed to be the result of different developmentally or environmentally caused disturbances involving the neural trajectories involved in information processing. Psychopathology and cognition will depend on the primary involvement of distinct parts of these circuits and on secondarily derived time-dependent disturbances of transmitter function. This review is focused on clinical and preclinical evidence for the impact of interactions between glutamatergic, dopaminergic, serotonergic and noradrenergic brain systems on cognitive performance. The hypothetical consequences of transmitter dysfunction for progressive development of impairment in sensorimotor gating are illustrated. Finally, the broad receptor profile of second generation antipsychotics is analysed to explain the clinical improvement in neurocognition that may occur during treatment with such drugs.
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Transtornos Cognitivos/etiologia , Neurotransmissores/fisiologia , Receptores de Neurotransmissores/fisiologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Antipsicóticos/uso terapêutico , Transtornos Cognitivos/fisiopatologia , Humanos , Neurônios/fisiologia , Transtornos Psicóticos/etiologia , Transtornos Psicóticos/fisiopatologia , Receptores Dopaminérgicos/fisiologia , Receptores de GABA/fisiologia , Receptores de Serotonina/fisiologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/etiologiaRESUMO
Information processing deficits are commonly found in psychiatric illnesses, while at the biochemical level serotonin seems to play a role in nearly all psychiatric disorders. Processing negativity (PN), mismatch negativity (MMN) and P300 amplitude are electrophysiological measures of information processing. The present study was designed to replicate and further extent the results of our initial study on the effects of a low dose of escitalopram (10 mg) on MMN, PN and P300 amplitude. In a randomised, double-blind, cross-over experiment, 20 healthy male volunteers received either a single, orally administered dose of 15 mg escitalopram (a highly selective serotonin reuptake inhibitor (SSRI)) or placebo, after which their PN, MMN and P300 amplitude were assessed. Similar to our initial study with 10 mg escitalopram, 15 mg escitalopram significantly increased MMN, while it did not affect P300 amplitude. In contrast to our initial study, however, the currently higher dose of escitalopram did not increase PN. Results support the view that a broad range of increased serotonergic activity enhances MMN, while the relationship between serotonin and PN seems more complex. The current study does not support a serotonergic involvement in P300 amplitude.